Infection and Drug Resistance (Jun 2021)
Synergistic Activity and Biofilm Formation Effect of Colistin Combined with PFK-158 Against Colistin-Resistant Gram-Negative Bacteria
Abstract
Liqiong Chen,1 Kaihang Yu,2 Lijiang Chen,1 Xiangkuo Zheng,1 Na Huang,1 Yishuai Lin,2 Huaiyu Jia,1 Wenli Liao,1 Jianming Cao,2 Tieli Zhou1 1Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Tieli Zhou Tel +86-577-86689885Email [email protected] Cao Tel +86-577-88069595Email [email protected]: The emergence of colistin resistance among Gram-negative bacteria (GNB) poses a serious public health threat. Therefore, it is necessary to enhance the antibacterial activity of colistin through the combination with other drugs. In this study, we demonstrated the synergistic activity and the possible synergy mechanism of colistin with PFK-158 against colistin-resistant GNB, including non-fermenting bacteria and Enterobacteriaceae.Patients and Methods: Thirty-one colistin-resistant GNB, including Pseudomonas aeruginosa (n = 9), Acinetobacter baumannii (n = 5), Escherichia coli (n = 8) and Klebsiella pneumoniae (n = 9), were collected as the experimental strains and the minimum inhibitory concentrations (MICs) of colistin, other routine antimicrobial agents and PFK-158 against all strains were determined by the broth microdilution method. The synergistic activity of colistin with PFK-158 was assessed by the checkerboard assay and time-kill assay. The biofilm formation assay and scanning electron microscopy were used to demonstrate the biofilm formation effect of colistin with PFK-158 against colistin-resistant GNB.Results: The results of the checkerboard assay showed that when colistin was used in combination with PFK-158, synergistic activity was observed against the 31 colistin-resistant GNB. The time-kill assay presented a significant killing activity of colistin with PFK-158 against the 9 colistin-resistant GNB selected randomly, including Pseudomonas aeruginosa (n = 6), Acinetobacter baumannii (n = 1), Escherichia coli (n = 1), and Klebsiella pneumoniae (n = 1). The biofilm formation assay and scanning electron microscopjihy showed that colistin with PFK-158 can effectively suppress the formation of biofilm and reduce the cell arrangement density of biofilm against most experimental strains.Conclusion: The results of the performed experiments suggest that the combination of colistin and PFK-158 may be a potential new choice as a new antibiofilm group for the treatment of infections caused by the colistin-resistant GNB.Keywords: synergy, non-fermenting bacteria, enterobacteriaceae, bacterial biofilm, cytotoxicity
